Different Molecular Mechanisms of Inhibition of Bovine Viral Diarrhea Virus and Hepatitis C Virus RNA-Dependent RNA Polymerases by a Novel Benzimidazole

Biochemistry ◽  
2013 ◽  
Vol 52 (21) ◽  
pp. 3752-3764 ◽  
Author(s):  
Shailendra Asthana ◽  
Saumya Shukla ◽  
Attilio V. Vargiu ◽  
Matteo Ceccarelli ◽  
Paolo Ruggerone ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Bovine Viral Diarrhea Virus ◽  
Molecular Mechanisms ◽  
Bovine Viral Diarrhea ◽  
Hepatitis C Virus Rna ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Virus Rna ◽  
Viral Diarrhea Virus

scholarly journals Development of a Cell-Based High-Throughput Specificity Screen Using a Hepatitis C Virus-Bovine Viral Diarrhea Virus Dual Replicon Assay

2005 ◽  
Vol 49 (4) ◽  
pp. 1346-1353 ◽  
Author(s):  
Donald R. O'Boyle ◽  
Peter T. Nower ◽  
Julie A. Lemm ◽  
Lourdes Valera ◽  
Jin-Hua Sun ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Throughput ◽  
Bovine Viral Diarrhea Virus ◽  
Bovine Viral Diarrhea ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Reporter Enzyme ◽  
Ns3 Protease ◽  
Viral Diarrhea Virus

ABSTRACT The hepatitis C virus (HCV) replicon is a unique system for the development of a high-throughput screen (HTS), since the analysis of inhibitors requires the quantification of a decrease in a steady-state level of HCV RNA. HCV replicon replication is dependent on host cell factors, and any toxic effects may have a significant impact on HCV replicon replication. Therefore, determining the antiviral specificity of compounds presents a challenge for the identification of specific HCV inhibitors. Here we report the development of an HCV/bovine viral diarrhea virus (BVDV) dual replicon assay suitable for HTS to address these issues. The HCV reporter enzyme is the endogenous NS3 protease contained within the HCV genome, while the BVDV reporter enzyme is a luciferase enzyme engineered into the BVDV genome. The HTS uses a mixture of HCV and BVDV replicon cell lines placed in the same well of a 96-well plate and isolated in the same cell backgrounds (Huh-7). The format consists of three separate but compatible assays: the first quantitates the amount of cytotoxicity based upon the conversion of Alamar blue dye via cellular enzymes, while the second indirectly quantitates HCV replicon replication through measurement of the amount of NS3 protease activity present. The final assay measures the amount of luciferase activity present from the BVDV replicon cells, as an indicator of the specificity of the test compounds. This HCV/BVDV dual replicon assay provides a reliable format to determine the potency and specificity of HCV replicon inhibitors.

scholarly journals Detection of Inhibition of Bovine Viral Diarrhea Virus by Aromatic Cationic Molecules

2003 ◽  
Vol 47 (7) ◽  
pp. 2223-2230 ◽  
Author(s):  
M. Daniel Givens ◽  
Christine C. Dykstra ◽  
Kenny V. Brock ◽  
David A. Stringfellow ◽  
Arvind Kumar ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Bovine Viral Diarrhea Virus ◽  
Specific Activity ◽  
Screening Method ◽  
Bovine Viral Diarrhea ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Viral Diarrhea Virus

ABSTRACT Bovine viral diarrhea virus (BVDV) is an economically significant pathogen of cattle and a problematic contaminant in the laboratory. BVDV is often used as an in vitro model for hepatitis C virus during drug discovery efforts. Aromatic dicationic molecules have exhibited inhibitory activity against several RNA viruses. Thus, the purpose of this research was to develop and apply a method for screening the aromatic cationic compounds for in vitro cytotoxicity and activity against a noncytopathic strain of BVDV. The screening method evaluated the concentration of BVDV in medium and cell lysates after 72 h of cell culture in the presence of either a 25 or 5 μM concentration of the test compound. Five of 93 screened compounds were selected for further determination of inhibitory (90 and 50%) and cytotoxic (50 and 10%) concentration endpoints. The screening method identified compounds that exhibited inhibition of BVDV at nanomolar concentrations while exhibiting no cytotoxicity at 25 μM concentrations. The leading compounds require further investigation to determine their mechanism of action, in vivo activity, and specific activity against hepatitis C virus.

scholarly journals Synergistic In Vitro Interactions between Alpha Interferon and Ribavirin against Bovine Viral Diarrhea Virus and Yellow Fever Virus as Surrogate Models of Hepatitis C Virus Replication

2003 ◽  
Vol 47 (7) ◽  
pp. 2293-2298 ◽  
Author(s):  
Victor E. Buckwold ◽  
Jiayi Wei ◽  
Michelle Wenzel-Mathers ◽  
Julie Russell
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Yellow Fever ◽  
Bovine Viral Diarrhea Virus ◽  
Yellow Fever Virus ◽  
Bovine Viral Diarrhea ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Viral Diarrhea Virus

ABSTRACT Monotherapy of hepatitis C virus infection with either alpha interferon or ribavirin alone is rather ineffective, while the use of the two antivirals together is much more efficacious. In vitro drug-drug combination analysis utilizing related members of the family Flaviviridae, bovine viral diarrhea virus and yellow fever virus, revealed significant direct synergistic interactions between these drugs' antiviral activities that might explain this clinical observation.

scholarly journals XRN1 Stalling in the 5’ UTR of Hepatitis C Virus and Bovine Viral Diarrhea Virus Is Associated with Dysregulated Host mRNA Stability

2015 ◽  
Vol 11 (3) ◽  
pp. e1004708 ◽  
Author(s):  
Stephanie L. Moon ◽  
Jeffrey G. Blackinton ◽  
John R. Anderson ◽  
Mary K. Dozier ◽  
Benjamin J. T. Dodd ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Bovine Viral Diarrhea Virus ◽  
Mrna Stability ◽  
Bovine Viral Diarrhea ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Viral Diarrhea Virus
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